Programmed cell death protein 1 and T-cell immunoreceptor with Ig and ITIM domains (PD-1 and TIGIT)

Programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) are inhibitory immune checkpoint receptors expressed on T cells, regulatory T cells, and NK cells. Upon engaging their respective ligands (PD-L1/PD-L2 for PD-1; CD155/PVR for TIGIT) on tumor or antigen-presenting cells, they transmit inhibitory signals that blunt immune cell activation, proliferation, and effector function, thereby enabling tumor cells to escape immune destruction. Blockade of these pathways—either individually or in combination—restores anti-tumor immunity and forms the basis for a growing class of immune checkpoint inhibitor drugs in cancer therapy. Recent clinical and mechanistic studies have shown that dual blockade of PD-1 and TIGIT yields superior activation of T cells, particularly through restoration of co-stimulatory CD226 signaling, compared to inhibition of either checkpoint alone. However, therapeutic challenges include management of immune-related toxicities and identification of patient subsets most likely to benefit from such therapies

Other names

CD279PDCD1WUCAMVstm3VSIG9

Immune checkpoint blockade: Antibody drugs inhibit the interaction of PD-1 with its ligand PD-L1 (and PD-L2), or TIGIT with PVR/CD155, restoring T cell (and NK cell) activation, cytokine production, and cytotoxicity against tumors. Combination therapies can lead to synergistic activation of anti-tumor immunity, especially by restoring co-stimulatory receptor signaling (CD28 and CD226) on T cells